Evaluating the Role of the Ocular Surface Microbiome in Dry Eye Disease Mediated Neural Dysregulation

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Brand, Cassandra
Microbiome , Dry eye disease , Opthalmology
Dry eye disease (DED) is a multifactorial ocular surface disorder arising from a loss of homeostasis at the corneal-tear interface. This leads to visual and neurosensory abnormalities which are regulated by the corneal-trigeminal ganglion pathway. An important contributor to ocular homeostasis is the ocular surface microbiome (OSM). In DED, the OSM has been postulated to be dysregulated, exhibiting a loss of diversity and increase in bacterial abundance. Along with evidence of roles for microbiota in regulating pain and neural activity, this has led to an emerging role for the OSM in the pathogenesis of DED. We sought to investigate how shifts in the OSM may be associated with neural dysregulation in DED. Using a newly described chronic mouse model of DED, we characterized the OSM using conjunctival swabs and culture-based techniques. Accompanying changes in neural activity were assessed using Ca2+ imaging on trigeminal ganglion (TG) neuron cultures derived from healthy and DED mice. Capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, was used to evaluate nociceptive changes in DED. Functional studies were complemented with morphological analyses of TRPV1 in the TG and cornea using qPCR and/or immunofluorescence. To assess the impact of microbes in DED mediated neural dysregulation, we manipulated the OSM in DED mice with topical administration of Gatifloxacin. Effects on the OSM and neural activity were monitored using conjunctival swabs and Ca2+ imaging, respectively. Our study showed that the OSM and neural activity were dysregulated in DED. In DED, we showed that the OSM was more abundant than controls and had a greater presence of potentially pathogenic strains of bacteria. Nociceptive responses in DED mice were diminished although no significant changes in the expression of TRPV1 were noted in the TG or cornea. This suggests that desensitization of TRPV1 may contribute to symptom presentation of DED. Although microbial changes support a role for the OSM in DED, a reduction in bacterial abundance was not shown to influence neural activity. Further manipulation studies are required to fully elucidate the role of the OSM in neural dysregulation with the hope of identifying the OSM as a novel therapeutic target.
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